title: Prediction of effective drug combinations by chemical interaction, protein interaction and target enrichment of KEGG pathways.
abstract: Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1) chemical interaction between drugs, (2) protein interactions between drugs' targets, and (3) target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations.
authors.affiliation: Institute of Systems Biology, Shanghai University, Shanghai 200444, China ; College of Information Engineering, Shanghai Maritime University, Shanghai 201306, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Bi-Qing
authors.initials: BQ
authors.lastname: Li
authors.forename: Ming-Yue
authors.initials: MY
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Feng
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Cai
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D004338:Drug Combinations; D004347:Drug Interactions; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012372:ROC Curve; D015398:Signal Transduction
chemical_list: D004338:Drug Combinations; D004364:Pharmaceutical Preparations; D011506:Proteins